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Updated: Apr 22, 2026

Assessment of Dictyostelium discoideum Response to Acute Mechanical Stimulation
Published on: November 9, 2017
Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium
Morgan N Thompson1, Marcy E MacDonald1, James F Gusella1
1Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Background:
The CAG triplet repeat expansion mutation in the HTT locus, which results in neurodegeneration in Huntington's disease, elongates a polyglutamine tract in huntingtin, a HEAT/HEAT-like protein that has been highly structurally conserved through evolution. In several organisms, huntingtin is necessary for proper cell-cell adhesion and normal development.
Objective:
Dictyostelium discoideum huntingtin null (htt-) cells display a variety of developmental abnormalities and completely fail to acquire EDTA-resistant homotypic cell adhesion during starvation in suspension culture.
Methods:
Here, we have assessed the hypothesis that htt may be a genetic interactor of csaA, a major regulator of EDTA-resistant homotypic cell adhesion in D. discoideum. Immunoblot analysis demonstrated that csaA protein expression is dysregulated in htt- cells.
Results:
Unexpectedly, csaA overexpression, previously shown to rescue csaA- cell adhesion, failed to rescue the htt- adhesion defect. Thus, while htt was required for proper expression of the csaA protein, csaA overexpression was not sufficient to confer EDTA-resistant adhesion in the context of the htt- genetic background in contrast to parental cells. This implies a novel role for htt in conferring csaA-dependent, EDTA-resistant cell adhesion that warrants further investigation. Calcium supplementation restored both endogenous csaA protein levels and EDTA-resistant adhesion in htt- cells.
Conclusions:
Our data suggests the existence of an additional mechanism that overcomes the EDTA-resistant adhesion defect of htt- cells in the early development of D. discoideum.
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